1. © 2016 Cengage Learning. All Rights Reserved. John E. McMurry www.cengage.com/chemistry/mcmurry Chapter 8 Alkenes: Reactions and Synthesis

2. © 2016 Cengage Learning. All Rights Reserved. Learning Objectives (8.1)  Preparing alkenes: A preview of elimination reactions (8.2)  Halogenation of alkenes: Addition of X 2 (8.3)  Halohydrins from alkenes: Addition of HOX (8.4)  Hydration of alkenes: Addition of H 2 O by oxymercuration (8.5)  Hydration of alkenes: Addition of H 2 O by hydroboration

3. © 2016 Cengage Learning. All Rights Reserved. Learning Objectives (8.6)  Reduction of alkenes: Hydrogenation (8.7)  Oxidation of alkenes: Epoxidation and hydroxylation (8.8)  Oxidation of alkenes: Cleavage to carbonyl compounds (8.9)  Addition of carbenes to alkenes: Cyclopropane synthesis (8.10)  Radical additions to alkenes: Chain-growth polymers

4. © 2016 Cengage Learning. All Rights Reserved. Learning Objectives (8.11)  Biological additions of radicals to alkenes (8.12)  Reaction stereochemistry: Addition of H 2 O to an achiral alkene (8.13)  Reaction stereochemistry: Addition of H 2 O to a chiral alkene

5. © 2016 Cengage Learning. All Rights Reserved. Diverse Reactions of Alkenes  Alkenes react with many electrophiles to give useful products by addition

6. © 2016 Cengage Learning. All Rights Reserved. Preparation of Alkenes: A Preview of Elimination Reactions  Alkenes are commonly made by elimination reaction  Dehydrohalogenation - Loss of HX from an alkyl halide  Occurs by reaction of an alkyl halide with strong base

7. © 2016 Cengage Learning. All Rights Reserved. Preparation of Alkenes: A Preview of Elimination Reactions  Dehydration - Loss of water from an alcohol  Carried out by treating an alcohol with a strong acid

8. © 2016 Cengage Learning. All Rights Reserved. Worked Example  How many alkene products, including E,Z isomers, might be obtained by dehydration of 3- methyl-3-hexanol with aqueous sulfuric acid?

9. © 2016 Cengage Learning. All Rights Reserved. Worked Example  Solution:  It is possible to obtain five alkene products by the dehydration of 3-methyl-3-hexanol

10. © 2016 Cengage Learning. All Rights Reserved. Halogenation of Alkenes: Addition of X 2  Halogenation - Bromine and chlorine add to alkenes to give 1,2-dihalides  Example  1,2-dichloroethane is formed by addition of Cl 2 to ethylene  Fluorine is too reactive and iodine does not react with majority of alkenes

11. © 2016 Cengage Learning. All Rights Reserved. Halogenation of Alkenes: Addition of X 2  Halogenation reaction of cycloalkane forms the trans stereoisomer of the dihalide addition product  Reaction occurs with anti stereochemistry

12. © 2016 Cengage Learning. All Rights Reserved. Mechanism of Bromine Addition  As suggested by George Kimball and Irving Roberts, for the observed stereochemistry the reaction intermediate is not a carbocation  Bromonium ion, R 2 Br +, is formed by electrophilic addition of Br + to the alkene

13. © 2016 Cengage Learning. All Rights Reserved. Mechanism of Bromine Addition  Bromonium ion is formed in a single step  Interaction of the alkene with Br 2 and simultaneous loss of Br -  Reaction with Br - ion occurs only from the opposite, unshielded side to give trans product

14. © 2016 Cengage Learning. All Rights Reserved. Mechanism of Bromine Addition  Bromonium ions were postulated more than 75 years ago to explain stereochemistry of halogen addition to alkenes  George Olah showed that bromonium ions are stable in liquid SO 2

15. © 2016 Cengage Learning. All Rights Reserved. Worked Example  Addition of HCl to 1,2-dimethylcyclohexene yields a mixture of two products  Show the stereochemistry of each, and explain why a mixture is formed  Solution:  Addition of hydrogen halides involves formation of an open carbocation

16. © 2016 Cengage Learning. All Rights Reserved. Worked Example  The carbocation, which is sp 2 -hybridized and planar, can be attacked by chloride from either top or bottom  This yields products in which the two methyl groups can be either cis or trans to each other

17. © 2016 Cengage Learning. All Rights Reserved. Halohydrins from Alkenes: Addition of HOX  Reaction of alkenes with hypohalous acids HO– Cl or HO–Br yields 1,2-halo alcohol, called a halohydrin  Addition takes place by reaction of the alkene with either Br 2 or Cl 2 in the presence of water

18. © 2016 Cengage Learning. All Rights Reserved. Figure 8.1 - Mechanism

19. © 2016 Cengage Learning. All Rights Reserved. Halohydrins from Alkenes: Addition of HOX  Bromohydrin formation is carried out in a solvent such as aqueous dimethyl sulfoxide, CH 3 SOCH 3 (DMSO), using the reagent N-bromosuccinimide (NBS)  Produces bromine in organic solvents and is a safer source

20. © 2016 Cengage Learning. All Rights Reserved. Worked Example  What product would you expect from the reaction of cyclopentene with NBS and water?  Show the stereochemistry  Solution:  –Br and –OH are trans in the product

21. © 2016 Cengage Learning. All Rights Reserved. Hydration of Alkenes: Addition of H 2 O by Oxymercuration  Hydration of an alkene is the addition of H 2 O to give an alcohol  Reaction takes place on treatment of the alkene with water and a strong acid catalyst

22. © 2016 Cengage Learning. All Rights Reserved. Figure 8.2 - Mechanism

23. © 2016 Cengage Learning. All Rights Reserved. Hydration of Alkenes: Addition of H 2 O by Oxymercuration  Acid-catalyzed hydration of isolated double bonds is uncommon in biological pathways  Fumarate is hydrated to give malate as one step in the citric acid cycle of food metabolism  In the laboratory, alkenes are often hydrated by the oxymercuration–demercuration procedure

24. © 2016 Cengage Learning. All Rights Reserved. Oxymercuration Intermediates  Reaction is initiated by electrophilic addition of Hg 2+ ion to the alkene  Gives an intermediate mercurinium ion  Regiochemistry of the reaction corresponds to Markovnikov addition of H 2 O

25. © 2016 Cengage Learning. All Rights Reserved. Worked Examples  What products would you expect from oxymercuration–demercuration of the following alkenes? a) b)  Solution:  Oxymercuration is equivalent to Markovnikov addition of H 2 O to an alkene a)

26. © 2016 Cengage Learning. All Rights Reserved. Worked Examples b)

27. © 2016 Cengage Learning. All Rights Reserved. Hydration of Alkenes: Addition of H 2 O by Hydroboration  Hydroboration: Process involving addition of a B–H bond of borane, BH 3, to an alkene to yield an organoborane intermediate, RBH 2  Boron has six atoms in its valance shell making borane a very reactive Lewis acid

28. © 2016 Cengage Learning. All Rights Reserved.  Alkene reacts with BH 3 in THF solution, rapid addition to the double bond occurs three times and a trialkylborane is formed  Net effect of the two-step hydroboration– oxidation sequence is hydration of the alkene double bond Hydration of Alkenes: Addition of H 2 O by Hydroboration

29. © 2016 Cengage Learning. All Rights Reserved. Hydration of Alkenes: Addition of H 2 O by Hydroboration  Regiochemistry that results when an unsymmetrical alkene is hydroborated makes the hydroboration reaction very useful  During hydroboration–oxidation of 1-methylcyclopentene, boron and hydrogen add to the alkene from the same face of the double bond with syn stereochemistry

30. © 2016 Cengage Learning. All Rights Reserved. Hydroboration  Differs from other alkene addition reactions  Occurs in a single step without a carbocation intermediate  Attachment of boron is favored  Non-Markovnikov regiochemistry occurs

31. © 2016 Cengage Learning. All Rights Reserved. Worked Example  What alkene might be used to prepare the following alcohol by hydroboration–oxidation?  Solution:  The products result from hydroboration/oxidation of a double bond  The –OH group is bonded to the less substituted carbon of the double bond in the starting material

32. © 2016 Cengage Learning. All Rights Reserved. Reduction of Alkenes: Hydrogenation  Hydrogenated: Addition of hydrogen to a double or triple bond to yield a saturated product  Reduction: Reaction that results in gain of electron density for carbon caused either by:  Formation between carbon and a less electronegative atom  Bond-breaking between carbon and a more electronegative atom

33. © 2016 Cengage Learning. All Rights Reserved. Reduction of Alkenes: Hydrogenation  Usually occurs with syn stereochemistry  H 2 is adsorbed onto the catalyst surface

34. © 2016 Cengage Learning. All Rights Reserved. Figure 8.5 - Mechanism

35. © 2016 Cengage Learning. All Rights Reserved. Reduction of Alkenes: Hydrogenation  Catalytic hydrogenation is extremely sensitive to the steric environment around the double bond  In α-pinene reduction occurs exclusively from the bottom face

36. © 2016 Cengage Learning. All Rights Reserved. Reduction of Alkenes: Hydrogenation  Catalytic hydrogenation is important in the food industry  Incomplete hydrogenation results in partial cis– trans isomerization of a remaining double bond  In biological hydrations, biological reductions occur in two steps:  Reducing agent, NADPH, adds a hydride ion to the double bond to give an anion  Anion is protonated by acid HA, leading to overall addition of H 2

37. © 2016 Cengage Learning. All Rights Reserved. Figure 8.7 - Reduction of the Carbon–Carbon Double Bond in Trans-crotonyl ACP

38. © 2016 Cengage Learning. All Rights Reserved. Worked Example  What products are obtained from catalytic hydrogenation of the following alkenes? a) b)

39. © 2016 Cengage Learning. All Rights Reserved. Worked Example  Solution: a) b)

40. © 2016 Cengage Learning. All Rights Reserved. Oxidation of Alkenes: Epoxidation and Hydroxylation  Oxidation: Reaction that results in a loss of electron density for carbon by:  Bond formation between carbon and a more electronegative atom  Bond-breaking between carbon and a less electronegative atom  Alkenes oxidize to give epoxides on treatment with a peroxyacid, RCO 3 H  Epoxide: Cyclic ether with an oxygen atom in a three-membered ring

41. © 2016 Cengage Learning. All Rights Reserved. Oxidation of Alkenes: Epoxidation and Hydroxylation  Peroxyacids transfer an oxygen atom to the alkene with syn stereochemistry  Treating a base with halohydrin leads to elimination of HX and production of an epoxide  Epoxides undergo an acid-catalyzed ring- opening reaction with water  Gives corresponding 1,2-dialcohol, or diol, also called a glycol  Net result of the two-step alkene epoxidation/hydrolysis is hydroxylation

42. © 2016 Cengage Learning. All Rights Reserved. Oxidation of Alkenes: Epoxidation and Hydroxylation  Hydroxylation can be carried out directly by treating an alkene with osmium tetroxide  Reaction occurs with syn stereochemistry  Does not involve a carbocation intermediate

43. © 2016 Cengage Learning. All Rights Reserved. Worked Example  What product is expected from reaction of cis-2- butene with metachloroperoxybenzoic acid?  Show the stereochemistry  Solution:  Epoxidation using m-chloroperoxybenzoic acid is a syn addition  Original bond stereochemistry is retained  The methyl groups are cis

44. © 2016 Cengage Learning. All Rights Reserved. Oxidation of Alkenes: Cleavage to Carbonyl Compounds  Ozone (O 3 ) adds to C═C bond, at low temperature, to form molozonide  Molozonide rearranges to form ozonide

45. © 2016 Cengage Learning. All Rights Reserved. Oxidation of Alkenes: Cleavage to Carbonyl Compounds  Ozonide is treated with a reducing agent to produce carbonyl compounds

46. © 2016 Cengage Learning. All Rights Reserved. Oxidation of Alkenes: Cleavage to Carbonyl Compounds  Oxidizing reagents other than ozone cause double-bond cleavage  Potassium permanganate (KMnO 4 ) can produce carboxylic acids and carbon dioxide if hydrogens are present on C═C

47. © 2016 Cengage Learning. All Rights Reserved. Oxidation of Alkenes: Cleavage to Carbonyl Compounds  Alkenes can be cleaved by hydroxylation to a 1,2-diol followed by reaction of a 1,2-diol with the periodic acid, HIO 4

48. © 2016 Cengage Learning. All Rights Reserved. Worked Example  What products would be expected from reaction of 1-methylcyclohexene with aqueous acidic KMnO 4 ?  Solution:  Aqueous KMnO 4 produces:  A carboxylic acid from a C═C  A ketone from a double bond carbon that is disubstituted

49. © 2016 Cengage Learning. All Rights Reserved. Addition of Carbenes to Alkenes: Cyclopropane Synthesis  Carbene, R 2 C: Neutral molecule containing a divalent carbon with only six electrons in its valence shell  Alkene addition is the reaction with a carbine to yield a cyclopropane  Added symmetrically across double bonds to form cyclopropanes

50. © 2016 Cengage Learning. All Rights Reserved. Figure 8.8 - Mechanism

51. © 2016 Cengage Learning. All Rights Reserved. Figure 8.9 - The Structure of Dichlorocarbene

52. © 2016 Cengage Learning. All Rights Reserved. Addition of Carbenes to Alkenes: Cyclopropane Synthesis  Addition of dichlorocarbene with cis-2-pentene is stereospecific  Stereospecific: Only a single stereoisomer is formed as product

53. © 2016 Cengage Learning. All Rights Reserved. Simmons-Smith Reaction  Method for preparing nonhalogenated cyclopropanes  Does not involve a free carbene  Utilizes a carbenoid  Reaction of diiodomethane with zinc-copper alloy produces zinc iodide  Yields corresponding cyclopropane in the presence of an alkene

54. © 2016 Cengage Learning. All Rights Reserved. Worked Example  What product is expected from the following reaction  Solution:  Reaction of a double bond with CH 2 I 2 yields a product with a cyclopropane ring that has a –CH 2 – group  Two different isomers can be formed, depending on stereochemistry of the double bond

55. © 2016 Cengage Learning. All Rights Reserved. Radical Additions to Alkenes: Chain-Growth Polymers  Polymer: Large molecule consisting of repeating units of simpler molecules, called monomers  Formed by polymerization  Alkenes react with radical catalysts to undergo radical polymerization  Simple alkene polymers are called chaingrowth polymers

56. © 2016 Cengage Learning. All Rights Reserved. Radical Additions to Alkenes: Chain-Growth Polymers

57. © 2016 Cengage Learning. All Rights Reserved. Radical Additions to Alkenes: Chain-Growth Polymers  Initiation  Few radicals are generated on heating a small amount of benzoyl peroxide catalyst  Benzoyloxy radical loses CO 2 and gives a phenyl radical

58. © 2016 Cengage Learning. All Rights Reserved. Radical Additions to Alkenes: Chain-Growth Polymers  Propagation  Radical from initiation adds to alkene to generate alkene derived radical  Process repeats to form the polymer chain  Termination  Chain propagation ends when two radical chains combine

59. © 2016 Cengage Learning. All Rights Reserved. Radical Additions to Alkenes: Chain-Growth Polymers  Other alkenes give other common polymers

60. © 2016 Cengage Learning. All Rights Reserved. Table 8.1 - Some Alkene Polymers and Their Uses

61. © 2016 Cengage Learning. All Rights Reserved. Worked Example  Show the monomer units required to prepare the following polymer:  Solution:  The smallest repeating unit in each polymer is identified and double bond is added  Monomer  H 2 C═CHOCH 3

62. © 2016 Cengage Learning. All Rights Reserved. Biological Additions of Radicals to Alkenes  Radical addition reactions have severe limitations in a laboratory environment  More controlled and more common than laboratory or industrial radical reactions

63. © 2016 Cengage Learning. All Rights Reserved. Figure 8.10 - Pathway of Biosynthesis of Prostaglandins from Arachidonic Acid

64. © 2016 Cengage Learning. All Rights Reserved. Reaction Stereochemistry: Addition of H 2 O to an Achiral Alkene  Majority of biochemical reactions yield products with chirality centers  1-Butene yields an intermediate secondary carbocation by protonation  It reacts with H 2 O from either the top or the bottom  The two transition states are mirror images

65. © 2016 Cengage Learning. All Rights Reserved. Figure 8.11 - Reaction of H 2 O with the Carbocation Resulting from Protonation of 1- Butene

66. © 2016 Cengage Learning. All Rights Reserved. Reaction Stereochemistry: Addition of H 2 O to an Achiral Alkene  Formation of a new chirality center by achiral reactants leads to a racemic mixture of enantiomeric products  Optically active product can only result by starting with an optically active reactant or chiral environment  Cis-aconitate is achiral  Only the enantiomer of the product is formed

67. © 2016 Cengage Learning. All Rights Reserved. Reaction Stereochemistry: Addition of H 2 O to a Chiral Alkene  The stereochemistry in acid-catalyzed addition of H 2 O is established by reaction of H 2 O with a carbocation intermediate  Does not contain a plane of symmetry  Chiral because of the chirality center at C4  Formation of a new chirality center by a chiral reactant leads to unequal amounts of diastereomeric products  Products are also optically active, if the chiral reactant is optically active because only one enantiomer is used

68. © 2016 Cengage Learning. All Rights Reserved. Figure 8.12 - Stereochemistry of the Acid- Catalyzed Addition of H 2 O to the Chiral Alkene

69. © 2016 Cengage Learning. All Rights Reserved. Worked Example  What products are formed from hydration of 4- methylcyclopentene?  Solution:

70. © 2016 Cengage Learning. All Rights Reserved. Summary  Bromine and chlorine add to alkenes via three- membered-ring bromonium ion or chloronium ion intermediates to give addition products having anti stereochemistry  If water is present during the halogen addition reaction, a halohydrin is formed  Oxymercuration–demercuration involves electrophilic addition of Hg 2+ to an alkene followed by subsequent treatment of the cation intermediate with NaBH 4

71. © 2016 Cengage Learning. All Rights Reserved. Summary  Hydroboration involves addition of borane followed by oxidation of the intermediate organoborane with alkaline H 2 O 2  Hydroboration–oxidation gives the product with non-Markovnikov syn stereochemistry  Catalytic hydrogenation is a process in which alkenes are reduced by addition of H 2 in the presence of a catalyst  Alkenes are oxidized by reaction with a peroxyacid to give epoxides

72. © 2016 Cengage Learning. All Rights Reserved. Summary  The corresponding cis-1,2-diols can be made directly from alkenes by hydroxylation with OsO 4  Alkenes react with divalent substances called carbenes, to give cyclopropanes  Nonhalogenated cyclopropanes are best prepared by a process called the Simmons– Smith reaction  Alkene polymers are formed by chain-reaction polymerization of simple alkenes